ΔNp63α is a common inhibitory target in oncogenic PI3K/Ras/Her2-induced cell motility and tumor metastasis

Significance Oncogenic hotspot mutations in PIK3CA or RAS and overexpression of Her2 are known as a driving force for human cancer development. We and others have shown that ΔNp63α, the major protein isoform of the p53-related p63 expressed in epithelial cells, functions as an important regulator for the cell adhesion program and is a critical inhibitor of cancer metastasis. In this study, we demonstrate that oncogenic p110α H1047R , K-Ras G12V , H-Ras G12V , and Her2 use a common Akt1-FOXO3a pathway in suppression of ΔNp63α expression and, consequently, promote cell migration/invasion and tumor metastasis. Thus, ΔNp63α may function as a critical integrator of oncogenic signals in cell motility and cancer metastasis.